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Expression of the NMDA receptor subunit GluN3A (NR3A) in the olfactory system and its regulatory role on olfaction in the adult mouse

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Abstract

Glutamate is an excitatory neurotransmitter in the olfactory system and its N-methyl-d-aspartate-(NMDA) receptor subunits [GluN1 (NR1), GluN2A (NR2A), and GluN2B (NR2B)] are expressed at synapses in the olfactory bulb and olfactory epithelium. Thus, glutamatergic neurons and NMDA receptors play key roles in olfaction. GluN3A (NR3A) is a unique inhibitory subunit in the NMDA receptor complex; however, the expression and functional role of GluN3A in the olfactory bulb and epithelium remain unclear. The present study examined the expression patterns of GluN3A in the olfactory bulb and epithelium and explored its functional role in the olfactory system. Immunohistochemical and Western blot analyses revealed that GluN3A is abundantly expressed in different cellular layers of the olfactory bulb and epithelium of the adult wild type (WT) mice. In littermate GluN3A knockout (GluN3A−/−; KO) mice, the expression of olfactory marker protein normally found in mature olfactory sensory neurons was significantly reduced in the olfactory bulb and epithelium. A butyl alcohol stimulus increased immediate-early gene c-Fos expression in the olfactory system of WT mice, while this response was absent in GluN3A KO mice. The level of phosphorylated Ca2+/calmodulin-dependent kinase II was significantly lower in GluN3A KO mice compared to WT mice. In buried food finding test, GluN3A mice took significantly longer time to find food compared to WT mice. Consistently, impaired odor distinguishing ability was seen in GluN3A KO mice. These findings suggest that GluN3A, expressed in the adult olfactory system, plays a significant regulatory role in olfactory development and functional activity.

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Abbreviations

NMDA:

N-methyl-d-aspartate

NMDAR:

NMDA receptor

WT:

Wild-type

KO:

Knockout

GluN1:

Glutamate NMDA receptor 1 (NR1)

GluN2:

Glutamate NMDA receptor 2A (NR2A)

GluN2B:

Glutamate NMDA receptor 2B (NR2B)

GluN3A:

Glutamate NMDA receptor 3A (NR3A)

GluN3B:

Glutamate NMDA receptor 3B (NR3B)

OMP:

Olfactory marker protein

ONL:

Olfactory nerve layer

GCL:

Granular cell layer

MCL:

Mitral cell layer

EPL:

External plexiform layer

GL:

Glomerular layer

CaMKII:

Ca2+/calmodulin-dependent kinase II

CREB:

CAMP response element-binding protein

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Acknowledgments

This work was supported by the NIH grants NS0458710 (SPY), NS075338 (LW), NS062097 (LW), NS073378 (TAD and SPY), and the American Heart Association grant AHA 12GRNT12060222 (SPY) and the AHA Established Investigator Award (LW).

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Authors and Affiliations

  1. Department of Anesthesiology, Emory University School of Medicine, 101 Woodruff Circle, WMB suite 620, Atlanta, GA, 30322, USA

    Jin Hwan Lee, Ling Wei, Todd C. Deveau, Xiaohuan Gu & Shan Ping Yu

  2. Department of Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Ling Wei

  3. Center for Visual and Neurocognitive Rehabilitation, VA Medical Center, Decatur, GA, 30033, USA

    Jin Hwan Lee, Xiaohuan Gu & Shan Ping Yu

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  1. Jin Hwan Lee
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  2. Ling Wei
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Correspondence to Shan Ping Yu.

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No human participants involved. All animal experiments and experimental protocols were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and were in compliance with National Institutes of Health (NIH) guidelines.

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Lee, J.H., Wei, L., Deveau, T.C. et al. Expression of the NMDA receptor subunit GluN3A (NR3A) in the olfactory system and its regulatory role on olfaction in the adult mouse. Brain Struct Funct 221, 3259–3273 (2016). https://doi.org/10.1007/s00429-015-1099-3

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